Objective: For most biologically relevant molecules their chirality
is decisive for their function. Within the last two decades asymmetric
organo-catalysis has emerged as an environmental benign, metal-free
alternative for conventional asymmetric transition metal catalysis. The
organo-catalysts, which employ catalyst-substrate interaction motifs
commonly found for enzymes, yield unprecedented enantiomeric excesses.
Despite the success of these organo-chemical routes, remarkably little
is known about the molecular details of the interaction between the
catalyst and the substrate. Consequently, there is virtually no
rationale method to optimize reaction conditions particularly as related
to structure-function relationships. Also the exact nature of the
intermediates that induce chirality has remained elusive. The aim of
this proposal is to experimentally quantify the formation of reaction
intermediates and the nature of intermediate induced chirality that lie
at the heart of asymmetric control. This will be achieved by using a
combination of advanced spectroscopic techniques. With advanced
vibrational spectroscopies (ultrafast two-color and two-dimensional
infrared spectroscopy), dielectric spectroscopy, and NMR spectroscopy
together with quantum chemical calculations we will quantify
structure-dependent interactions: binding geometry, strength of
attraction, lifetime of binding, reaction intermediates, and the role of
steric repulsion, probed on all timescales relevant to catalytic
processes ranging from femtoseconds to seconds. Correlation of such
information with the enantiomeric excess obtained in catalytic processes
will allow isolating the essential ingredients for stereocontrol. Such
molecular-level insights will provide fundamental parameters for
optimization of reaction conditions and will initiate the transition
from a trial and error approach towards a rational design of new
catalytic processes.